The laminitis mystery is far from solved, but researchers continue to discover new clues about its causes, treatment, and prevention.

Laminitis, an often devastating hoof disease that can strike horses of any breed without warning, is a major issue for horse owners and veterinarians alike. In the recent American Horse Publications (AHP) Equine Industry Survey, nearly 50% of the 11,000-plus owners surveyed listed it as a health issue of concern. And in last year's AAEP (American Association of Equine Practitioners) Equine Research study, 63% of the responding veterinarians listed it as a health condition in need of more research, making it the No. 1 health problem listed on the survey.

Some of the best minds in equine veterinary medicine have targeted this disease, and the pieces are starting to fall into place. Here we'll visit studies described by James Orsini, DVM, Dipl. ACVS, Penn Vet Laminitis Institute director; and Amy Rucker, DVM, of Midwest Equine in Columbia, Mo., who both presented at the Fifth International Equine Conference on Laminitis and Diseases of the Foot (Nov. 6-8, 2009).

Laminitis Basics

Laminitis is an inflammation of the laminae--interlocking leaflike tissues attaching the hoof to the coffin bone. It can strike any number of feet on any horse due to a variety of triggers, from high-carbohydrate diets in sensitive horses to colic to retained placenta to mechanical overload. Severity ranges from mild and curable to severe and incurable (resulting in euthanasia).

Enzymes and the Laminitis Process

A major focus in laminitis research has been enzymes (which catalyze or stimulate chemical reactions in the body) that get out of balance in early stages of the disease. It's been theorized that if these enzymes could be controlled medically, laminitis could be prevented or minimized. Previous work has often focused on enzymes called matrix metalloproteinases (MMPs), which have a role in hoof growth but become overactive in laminitis. However, more recent work has found that another enzyme, an aggrecanase termed ADAMTS-4, spikes much earlier in the laminitic diseaseprocess than MMPs (first reported by Orsini and colleagues at Penn in 2005).

Christopher Pollitt, BVSc, PhD, director of the Australian Equine Laminitis Research Unit and research director of the Penn Vet Laminitis Institute, wrote that these findings "are causing us to rethink the early events that culminate in clinical signs of laminitis." Another researcher, Samuel Black, PhD, professor of Veterinary and Animal Sciences at the University of Massachusetts, discussed similar ADAMTS-4 findings, lending support to this line of research.

Black also reported that certain molecules that help joint cartilage resist compressive forces (the proteoglycans: aggrecan and versican) have recently been found in the laminae, suggesting a similar role there. Thus, increased activity of the ADAMTS-4 enzyme that breaks down these molecules "may contribute to the loss of lamellar function in laminitis," he noted.

Hormones and Laminitis

Overweight horses are at higher risk for laminitis, often due to insulin resistance (a reduction in sensitivity to insulin that -decreases the ability of glucose to be transported into the body's cells from the bloodstream). Nicholas Frank, DVM, PhD, Dipl. ACVIM, associate professor of Large Animal Medicine at the University of Tennessee, noted insulin resistance can "lower the threshold" for laminitis in affected horses.

He also noted small management changes, such as introducing a new batch of hay or feed with higher levels of nonstructural carbohydrates (NSC), stress increases, or exercise reduction, can push these horses over the edge. Frank reported that even healthy horses hospitalized for two weeks had increased insulin resistance, suggesting that stress and possibly exercise reduction can contribute to insulin resistance.

"We haven't had any studies to support this in the past," noted Orsini.

Nutrition and Pasture Management

Horses with high body condition scores (7-9, fleshy to extremely fat; see www.TheHorse.com/pdf/nutrition/bcs.pdf for more on body condition scores), hyperinsulinemia (high levels of insulin in the bloodstream of 32mU/L or more), and cresty necks "are the ones you should look at very carefully, as these are good predictive criteria for laminitis development under certain conditions," said Orsini. This research was presented by Ray Geor, MVSc, PhD, Dipl. ACVIM, professor and chairperson of the Department of Large Animal Clinical Sciences at Michigan State University.

For these at-risk horses, Geor recommended reducing digestible energy in the diet, keeping NSC levels in grass hay at 10% or less (see "Analyzing Forages" at www.TheHorse.com/6172), removing grain from the diet, feeding hay at 1.5% of the horse's body weight per day or less, eliminating pasture grass access until the horse is no longer overweight, and increasing exercise to improve insulin sensitivity.

"Prevention is still the best course of (laminitis) treatment," stated Orsini.

In another presentation a researcher reported that regional weather conditions are more important than grass type or even overall season when it comes to NSC content in pastures. Kathryn Watts, BS, of Rocky Mountain Research and Consulting, reported that when comparing established, matched stands of several grass species in Colorado and Utah throughout the year, the samples from cooler, sunnier Colorado were always higher in NSC by up to 8%. Cool temperatures (below 40°F at night), sunny weather, drought stress, fall rains/cool temperatures (increased growth), and frost stress can all increase NSC concentrations, she added.

"She has also told us that it may be safer to turn an at-risk horse out on winter pasture after snow covers the ground and leaches out some of the sugars from the grass," recalled Rucker.

Lastly in the nutrition area, Pollitt reported that the laminae appear to depend more on anaerobic (without oxygen) energy metabolism. Thus, they consume a good deal of glucose; Pollitt discussed using an open-centered (cannulated) screw through the hoof wall to help deliver glucose and medications directly to the laminae.

Medications

Pentoxifylline Susan Eades, DVM, PhD, Dipl. ACVIM, a professor of Veterinary Clinical Sciences at Louisiana State University, reported that of the medications doxycycline, oxytetracycline, pentoxifylline, and flunixin meglumine, pentoxifylline was the most potent inhibitor of MMP production. She also noted that in a small study, horses given pentoxifylline every 12 hours after dosing with excessive carbohydrate (to induce laminitis) were one to two grades less lame than controls, and in some cases they did not become lame at all.

Pain medications Tony Yaksh, PhD, vice chair of Anesthesiology at the University of California, San Diego,discussed the possibility that the pain of laminitis might represent not only the pain of the disease, but also hypersensitized nerve pain termed neuropathic pain. Normally associated with "complex pain states" such as those in arthritis, osteosarcoma, and diabetes, this neuropathic pain does not always respond completely to pain medications directed toward other mechanisms of pain.

"He challenged us to think about whether we should be treating for both types of pain, not just one or the other," recalled Orsini.

Inflammation

Investigating inflammatory processes is another major focus in laminitis research. James Belknap, DVM, PhD, Dipl. ACVS, a professor of Veterinary Clinical Sciences at The Ohio State University, discussed several ongoing projects in this area with the following findings:

The two main laminitis models used for study, which include the carbohydrate overload model mentioned above and a model whereby researchers use black walnut extract to induce laminitis, both cause inflammation in the laminae. However, the times at which the inflammation arises, and the particular inflammatory mediators that the researchers see, vary between the models.

While oxidant stress (damage from free radicals) does occurwith laminitis, it appears to be controlled and, thus, not a significant cause of structural failure.

Although white blood cells were thought only to be present in the laminae when laminar damage occurred, Belknap reported they also have been found in normal laminae. The number of white blood cells of different types does increase in the laminae with laminitis, but to different degrees depending on the model.

Since certain white blood cells in large amounts could contribute to laminar damage, inhibiting them could help reduce laminitis severity. Belknap reported that nonspecific cyclo-oxygenase (COX) inhibitors might be indicated for initial laminitis treatment, and COX-2 inhibitors might be better for long-term use in chronic cases. Anti-inflammatory drugs such as corticosteroids inhibit white blood cell activity and might also be worth considering, but until this use for them is studied, sticking to non-steroidal anti-inflammatory medications such as phenylbutazone (Bute), flunixin meglumine (Banamine), and firocoxib (Equioxx), as prescribed by your veterinarian, is best.

Rucker presented a "diagnostic multimedia" approach that included taking a detailed history, conducting a physical exam, radiography, digital venography, and MRI when available to determine the degree of damage and develop an effective treatment plan.

"As our understanding of the soft tissue pathology in laminitic horses improves, enhanced use of traditional technology and adaptation of newer technology offers the opportunity to detect the changes and implement appropriate treatment much earlier in the disease process when treatment response is optimum," she noted. "You have to have mechanical collapse of the foot (to some degree) even before you can see measurement changes on a radiograph, but you can see major changes earlier on venograms and MRI imaging." (More information on imaging protocols: Clinical and Radiographic Examination of the Equine Foot, www.TheHorse.com/1457)

Treatment Options

TenotomyCutting the deep digital flexor tendon to remove its pull on the diseased laminae is often a last resort, but some practitioners have found it to be very effective when used early. Scott Morrison, DVM, of Rood & Riddle Equine Hospital in Lexington, Ky., discussed a 245-horse retrospective study of tenotomy cases and reported success rates (pasture soundness at minimum) as high as 93%, depending on the case. Sinkers (the coffin bone sinks straight down in the hoof capsule without its tip rotating down toward the sole) had the lowest success rate at 18%.

"Deep digital flexor tenotomy accompanied by realignment shoeing improves the outcome in horses with chronic laminitis that are unresponsive to shoeing alone," said Morrison.

Cold therapyCryotherapy was shown to prevent laminitis in high-risk cases years ago, but today there's still no commercial system in widespread use due to technical challenges. At the conference, Andrew van Eps, BVSc, PhD, MACVSc, Dipl. ACVIM, senior lecturer in Equine Medicine at the University of Queensland, discussed a study using a system in which a membrane stays in contact with the lower leg and foot while coolant constantly circulates over it. He reported that this type of system was effective at keeping the foot near the target temperature of 5°C (41°F).

Moving Forward

The second annual Laminitis West conference, also organized by the Penn Vet Laminitis Institute, will take place Sept. 17-18, 2010, in Monterey, Calif., and is open to anyone. For more information, see www.laminitisconference.com.

Expect to see more groundbreaking discoveries from the researchers who are working tirelessly to knock laminitis off its No. 1 horse health problem pedestal.

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